PROJECT SUMMARY/ABSTRACT The transformative impact of transition metal-catalyzed cross-coupling is well recognized. In the archetypal palladium-catalyzed Suzuki or Hiyama biaryl cross-coupling reactions, a three step catalytic cycle mechanistically based on oxidative addition of an aryl halide at Pd0, transmetalation of the organometallic nucleophile with an arylpalladium(II) species, and reductive elimination, which releases the biaryl product and regenerates the Pd0 catalyst. Although such methods are highly effective for Csp2-Csp2 coupling, extension to 2 and 3 Csp3 centers has proven challenging, owing primarily to lower rates of transmetalation as well as the propensity of the alkylpalladium intermediates to undergo facile ?-hydride elimination. Despite recent progress, challenges remain with the nucleophilic component of alkyl cross-couplings, because the nature of the transmetalation has remained principally unchanged since the inception of cross-coupling chemistry. As such, transmetalation is rate limiting in organoboron and organosilicon protocols operating under the traditional mechanistic manifold, providing severe restrictions on the scope of these processes. To date, strategies aimed at facilitating the transmetalation of Csp3 Suzuki cross-couplings are uniformly rudimentary and largely ineffective. Often, the only alternative is to abandon these approaches and utilize more reactive organometallic reagents such as organozincs, -magnesiums, or ?stannanes, which lack bench stability, severely limit functional group tolerability, are considered toxic, and/or are challenging to access in enantiopure form. The limitations of the transmetalation in the more desirable Suzuki and Hiyama couplings are inherent to the mechanism of these processes at the most fundamental level, and thus predispose alkylborons and alkylsilicons for failure in cross-coupling. The goal of the research described herein is to demonstrate that a novel single electron mechanistic paradigm for transmetalation in cross-coupling, in which dual catalytic cycles are established, will circumvent deficiencies in current cross-coupling protocols. Thus, a photoredox catalytic cycle, generating radicals from nucleophilic organometallic species, can funnel these radicals into a base metal catalytic cycle that effects the cross-coupling. The single electron transfer (SET) mediated transmetalation that results will succeed in cases where the traditional two-electron pathway fails by exhibiting reactivity trends complementary to traditional cross-coupling, with 2 and 3 Csp3 nucleophiles now ideally primed for successful implementation. As a result, nearly all cross-couplings will be engineered to be successful using bench-stable, robust reagents and base metal catalysts under conditions (e.g., ambient temperatures, neutral pH) that will allow maximum tolerability of sensitive, unprotected functional groups, even with demanding 2 and 3 Csp3- hybridized nucleophiles.